A Modular Phase 2a Multicentre Open-Label Study to Investigate DNA-damage Response Agents (or Combinations) in Patients With Advanced Cancer Whose Tumours Contain Molecular Alterations (PLANETTE)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Cohort A (aST): Objective Response Rate (ORR).
研究概览
简要总结
The study is investigating efficacy, safety and tolerability of DNA-damage Response Agents (or Combinations), in participants with advanced/metastatic solid malignancies whose tumours contain molecular alterations
详细描述
Current module of the study will consist of 2 cohorts as follows:
Cohort A (Advanced Solid Tumours [AST]): A total of ~25 molecularly eligible and centrally confirmed participants dosed at ceralasertib 160 mg twice daily will be enrolled into this cohort.
Cohort B (Metastatic castration-resistant prostate cancer [mCRPC]): A total of ~27 molecularly eligible and centrally confirmed participants dosed at ceralasertib 160 mg twice daily will be enrolled into Cohort B. Unfavourable circulating tumour cells (CTC) count requirement may be introduced for all participants to ensure an adequate (approximately ≥ 50%) number of participants with CTC count ≥ 5/7.5 mL blood.
The screening will have 2 parts, Part 1 and Part 2, which apply for both Cohort A and Cohort B.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have a histologically confirmed diagnosis of AST (excluding NSCLC) or mCRPC tumour.
- •Participants must have a deleterious or suspected deleterious ATM mutation in tumour or blood (germline or ctDNA). Definitions of qualifying ATM mutations may include deleterious/suspected deleterious, pathogenic/likely pathogenic, disease- or cancer-associated variants, or equivalent wording. Variants of unknown significance, benign or likely benign alterations are not qualifying.
- •Participant must have normal organ and bone marrow function measured within 28 days prior to the first dose of study intervention.
- •Participants who have no curative treatment options and are deemed appropriate for an investigational study in the opinion of the investigator.
- •Availability of archival or fresh tumour specimens for central testing of ATM protein loss using immunohistochemistry and for confirmation of ATM mutation using next generation sequencing.
- •Previously received and progressed on at least one novel hormonal agent (eg, abiraterone acetate, apalutamide, and/or enzalutamide) for the treatment of prostate cancer
- •Participants with histologically confirmed metastatic castrate resistant prostate cancer.
- •Documented prostate cancer progression at study entry while on androgen deprivation or after bilateral orchiectomy as assessed by the investigator.
- •Serum testosterone levels ≤ 50 ng/dL (≤ 1.75 nmol/L) within (≤) 28 days before enrolment.
排除标准
- •Any of the following cardiac diseases currently or within the last 6 months:
- •Unstable angina pectoris.
- •Congestive heart failure > Class 2 as defined by the New York Heart Association
- •Acute myocardial infarction.
- •Significant ventricular or supraventricular arrhythmias.
- •Mean resting corrected QT interval (QTc) > 470 msec obtained from three electrocardiograms (ECGs) in 24 hours using the Fredericia formula.
- •Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, immediate family history of long QT syndrome or unexplained sudden death under 40 years of age.
- •For Cohort B (mCRPC]), surgery or local prostatic intervention (excluding a prostatic biopsy) within 28 days of Cycle 1 Day
- •Participants with known active infections ((i.e., hepatitis B or C, tuberculosis, or COVID-19).
- •Participants considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
- •Participants with symptomatic and/or uncontrolled brain metastases.
- •Previous therapy with an telangiectasia and rad3 related protein inhibitor.
- •Exposure to a small molecule investigational product within 14 days or 5 half-lives.
- •Concomitant use of known strong CYP 3A inhibitors and inducers.
研究组 & 干预措施
Cohort A
Eligible participants (ATM altered AST), will receive oral dose of Ceralasertib as monotherapy.
干预措施: Ceralasertib (Drug)
Cohort B
Eligible participants (ATM altered mCRPC), will receive oral dose of Ceralasertib as monotherapy.
干预措施: Ceralasertib (Drug)
结局指标
主要结局
Cohort A (aST): Objective Response Rate (ORR).
时间窗: 2 years 4 months
ORR is defined as the percentage of participants who have at least one response of complete response (CR) or partial response (PR) prior to any evidence of progression (as defined by response evaluation criteria in solid tumours \[RECIST\] 1.1) that is confirmed at least 4 weeks later. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline and no new non-target lesion. Due to an increased frequency and early onset of Grade≥3 hematological toxicity noted among the participants receiving 240 mg of Ceralsertib, the sponsor decreased the dose to 160mg. Therefore, patients with the 240 mg BID starting dose were not included in the efficacy analyses for both study cohorts.
Cohort B (mCRPC): Composite Response Rate.
时间窗: Up to 2 years 4 months
Composite response rate is defined as the investigator assessed radiological response by RECIST 1.1 for soft tissue and visceral lesions and Prostate Cancer Working Group 3 (PCWG3) for bone lesions, confirmed prostate specific antigen (PSA) decline of more than 50%, and/or confirmed circulating tumour cell \[CTC\] conversion from unfavorable (\>=5 cells/7.5 ml blood) to favorable (\<5 cells). Due to an increased frequency and early onset of Grade≥3 hematological toxicity noted among the participants receiving 240 mg of Ceralsertib, the sponsor decreased the dose to 160mg. Therefore, patients with the 240 mg BID starting dose were not included in the efficacy analyses for both study cohorts.
次要结局
- Cohort A (aST): Percentage Change in Tumor Size(Scan Visits 1 (Week 8), 2 (Week 16), 3 (Week 24), 4 (Week 32), 5 (Week 40), 6 (Week (48), 7 (Week 56))
- Cohort A (aST) and B (mCRPC): Number of Participants With Serious and Non-serious Adverse Events(From Screening (Day -28 to Day -1) Until Follow-up (30 days post last dose), up to 2 years 4 months)
- Cohort B (mRCPC): Percentage Change in Tumor Size(Scan Visits 1 (Week 8), 2 (Week 16), 3 (Week 24), 4 (Week 32))
- Cohort A (aST): Duration of Radiological Response (DoR)(Up to 2 years 4 months)
- Cohort A (aST): Progression Free Survival (PFS)(Up to 2 years 4 months)